新生儿睾丸发育不全综合征的发病率不断攀升，与孕期胎儿雄激素不足或失调相关。全氟辛烷磺酸（PFOS）为重要的环境污染物，生殖系统毒性备受关注。我们前期研究发现PFOS能干扰睾丸间质干细胞（SLC）的增殖和分化，致睾丸间质细胞发育障碍而影响雄激素生成，但机制未明。同时发现糖原合酶激酶-3β（GSK-3β）参与SLC发育。而GSK-3β是糖原合成最后关键酶，参与Wnt等大量信号转导途径。因此提出假说：PFOS可能通过调控GSK-3β磷酸化及下游信号分子，抑制SLC增殖和分化。本课题以PFOS调控GSK-3β磷酸化为切入点，通过在体研究及离体不同时相GSK-3β通路的siRNA和小分子抑制剂干预，研究PFOS对睾丸间质细胞发育影响的分子信号通路，阐明孕期和哺乳期PFOS暴露对胎儿睾丸发育的损伤作用机理，为新生儿生殖系统发育毒性作用机制研究和新靶点治疗提供理论基础和科学依据。

Neonatal testicular hypoplasia syndrome incidence continues to rise, and is related to pregnancy androgen deficiency or disorders. Perfluorooctane sulfonate (PFOS) is an important environmental pollutant, its toxicity to reproductive system is concerned. Our previous study found that PFOS can interfere with the proliferation and differentiation of testicular stem Leydig cells (SLC), resulting in testicular interstitial Leydig cell development obstacle and affect the androgen formation, but the mechanism is unknown. We also found that glycogen synthase kinase-3β (GSK-3β) was involved in SLC development. GSK-3β is the last key enzyme in glycogen synthesis, and it participates in a large number of signal transduction pathways such as Wnt. Therefore, it is hypothesized that PFOS may inhibit SLC proliferation and differentiation by regulating GSK-3β phosphorylation and downstream signaling molecules. In this study, using PFOS to regulate GSK-3β phosphorylation as the entry point, and the molecular signaling pathway of PFOS on the development of testicular Leydig cells was studied by siRNA and small molecule inhibitor intervention in GSK-3β pathway in vivo and in vitro. By elucidating the mechanism of PFOS exposure during pregnancy and lactation on the development of fetal and neonatal testes, this study will provide theoretical basis and scientific proof for the mechanism of neonatal reproductive system development toxicity and new target therapy.